Sorafenib Triggers Antiproliferative and Pro-Apoptotic Signals in Human Esophageal Adenocarcinoma Cells
Background and purpose Current therapies offer scant benefit to patients with advanced esophageal adenocarcinoma. We investigated the effects of Sorafenib, a multifunctional kinase inhibitor, on several growth regulatory pathways that control cell growth and survival in SEG-1 cells derived from Barr...
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Published in | Digestive diseases and sciences Vol. 53; no. 12; pp. 3055 - 3064 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.12.2008
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Background and purpose
Current therapies offer scant benefit to patients with advanced esophageal adenocarcinoma. We investigated the effects of Sorafenib, a multifunctional kinase inhibitor, on several growth regulatory pathways that control cell growth and survival in SEG-1 cells derived from Barrett’s adenocarcinoma.
Methods
SEG-1 cells were exposed to acidified medium or taurocholic acid, with and without pre-incubation with Sorafenib. Cyclin D1 and E, c-Myc, and Bcl-2 expression levels as well as STAT3 activations were determined by Western blotting. Cyclin D1 mRNA was measured by real-time PCR. Apoptosis was assessed by TUNEL assay.
Results
Sorafenib significantly inhibited SEG-1 cell proliferation stimulated by acid or bile acid treatments and reduced cell survival. This drug significantly reduced the up-regulations of cyclin D1, cyclin E, c-Myc, and Bcl-2 as well as the activation of STAT3 in SEG-1 cells.
Conclusions
These results support a rational basis for future clinical studies to assess the therapeutic benefit of Sorafenib in esophageal adenocarcinoma. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0163-2116 1573-2568 |
DOI: | 10.1007/s10620-008-0294-y |